The immune landscape of hepatocellular carcinoma‑where we are? (Review)

Abstract

Hepatocellular carcinoma (HCC) is one of the most common types of cancer diagnosed worldwide. After a decade of stagnation, several novel compounds have recently been shown to be effective in the treatment of HCC. Since immunotherapy is associated with important clinical benefits in some, but not all patients, it is essential to identify reliable predictive biomarkers. As the complex interplay between hepatocytes and immune cells is highly dependent on the tumor microenvironment, the tumor microenviroment has been suggested to be an important factor associated with the response to therapy and is currently being extensively investigated. Within this network, several important factors should be highlighted. Most of the cells are hepatocytes, but fibroblasts, endothelial cells, and immune cells are also present. Tumor-infiltrating leukocytes include several populations of cells and each of them plays a role in forming the tumor environment. Some of these cells may have antitumor effects, whereas others may be associated with the progression of the disease. The most important subsets include tumor-associated macrophages, tumor-associated neutrophils, and lymphocytes. These groups are described in the present review. The immune response is controlled by immune checkpoint molecules. One of the most important molecules involved in this checkpoint process seems to be the programmed death-1 (PD-1) receptor, which typically is induced on activated T cells, natural killer (NK) cells, B cells, and antigen-presenting cells. On the other hand, programmed death ligand 1 (PD-L1) is expressed by tumor cells, hepatocytes and hepatic stellate cells, and Kupffer cells or liver sinusoidal cells. Complex interactions between ligands and receptors are dependent on the signals from the microenvironment leading to either cancer development or apoptosis. Evidence from several studies indicates that patients with higher expression levels of PD-L1 on tumor cells or immune cells are more likely to achieve beneficial results from treatment with checkpoint blockers. This review focuses on the basic information regarding the microenvironment and its components, particularly on immune system involvement. Contents 1. Introduction 2. Myeloid-derived suppressor cells (MDSCs) 3. Tumor-associated macrophages (TAMs) 4. Tumor-infiltrating leukocytes (TILs) 5. Tumor-associated neutrophils (TANs) 6. Tumor microenvironment and response to systemic treatment 7. Immune checkpoint inhibition 8. Immune checkpoint inhibitors assessed for treatment of HCC 9. Immune microenvironment factors associated with the response to immunotherapy 10. Additional potential biomarkers and predictive factors for the response to immunotherapy 11. Conclusions

GEO data mining identifies potential immune-related genes in hypertrophic scar and verities in a rabbit model

“…We also found evidence underlying the numerical correlation between immune cell infiltrates in HTS, such as CD4 T cells (memory and resting) and CD8 T cells, resting and activated NK cells, and monocytes and macrophages M0. Some of these have been previously reported and others remain to be confirmed [ [21] , [22] , [23] ]. We compared the differences in immune infiltrating cell composition between HTS and normal tissues.…”

Clinical significance of FBXO43 in hepatocellular carcinoma and its impact on tumor cell proliferation, migration and invasion

“…Recently, immunotherapy has become a novel first-line treatment choice for advanced HCC ( Hilmi et al, 2019 ; Laface et al, 2022 ; Sangro et al, 2021 ). Studies have shown that infiltrating immunocytes in tumor tissue can interact with tumor cells and affect tumor progression, and can affect the prognosis of patients ( Dong et al, 2016 ; Gryziak et al, 2022 ; Pham et al, 2022 ; Sia et al, 2017 ). In particular, reports indicate that immunosuppressive tumor microenvironment due to tumor immunocyte infiltration can lead to poor prognosis ( Hoechst et al, 2008 ; Khanam & Kottilil, 2022 ).…”

Deciphering hepatocellular carcinoma pathogenesis and therapeutics: a study on anoikis, ceRNA regulatory network and traditional Chinese medicine

“…In the context of HCC, M1 polarized macrophages can impede tumor growth through various pathways, while their M2 counterparts are involved in promoting angiogenesis, which facilitates tumor development (Cheng et al, 2022). Neutrophils have a dualistic role in oncogenesis, as they can either stimulate or inhibit cancer progression, highlighting their complex relationship with tumor pathobiology (Gryziak et al, 2022). NK cells are known for their innate cytotoxic potential and play a crucial role in lymphocytemediated effector responses.…”